title: Structural alterations and changes in cytoskeletal proteins and proteoglycans after focal cortical ischemia.
abstract: In order to study structural alterations which occur after a defined unilateral cortical infarct, the hindlimb region of the rat cortex was photochemically lesioned. The infarcts caused edema restricted to the perilesional cortex which affected allocortical and isocortical areas differently. Postlesional changes in cytoskeletal marker proteins such as microtubule-associated protein 2, non-phosphorylated (SMI32) and phosphorylated (SMI35, SMI31 and 200,000 mol. wt) neurofilaments and 146,000 mol. wt glycoprotein Py as well as changes in proteoglycans visualized with Wisteria floribunda lectin binding (WFA) were studied at various time points and related to glial scar formation. The results obtained by the combination of these markers revealed six distinct regions in which transient, epitope-specific changes occurred: the core, demarcation zone, rim, perilesional cortex, ipsilateral thalamus and contralateral homotopic cortical area. Within the core immunoreactivity for microtubule-associated protein 2 and SMI32 decreased and the cellular components showed structural disintegration 4 h post lesion, but partial recovery of somatodendritic staining was seen after 24 h. Microtubule-associated protein 2 and SMI32 persisted up to days 7 and 5 respectively in the core, whereas the number of glial fibrillary acidic protein- and WFA-positive cells decreased between days 7 and 14. The demarcation zone showed a dramatic loss of immunoreactivity for all epitopes 4 h post lesion which was not followed by a phase of recovery. In the inner region of the demarcation zone there was an invasion and accumulation of non-neuronal WFA-positive cells which formed a tight capsule around the core. Neuronal immunoreactivities for microtubule-associated protein 2, SMI31 and Py as well as astrocytic glial fibrillary acidic protein increased strongly within an approximately 0.4-1.0 mm-wide rim region directly bordering the demarcation zone. Py immunoreactivity increased significantly in the perilesional cortex, whereas glial fibrillary acidic protein-positive astrocytes became transiently more numerous in the entire lesioned hemisphere including strongly enhanced immunoreactivity in the thalamus by days 5-7 post lesion. Glial fibrillary acidic protein immunoreactivity increased in the corpus callosum and the homotopic cortical area of the unlesioned hemisphere by days 5-7. In this homotopic area additional changes in SMI31 immunoreactivity occurred. Our results showed that a cortical infarct is not only a locally restricted lesion, but leads to a variety of cytoskeletal and other structural changes in widely-distributed functionally-related areas of the brain.
authors.affiliation: Department of Neuroanatomy, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Bidmon
authors.forename: V
authors.initials: V
authors.lastname: Jancsik
authors.forename: A
authors.initials: A
authors.lastname: Schleicher
authors.forename: G
authors.initials: G
authors.lastname: Hagemann
authors.forename: O W
authors.initials: OW
authors.lastname: Witte
authors.forename: P
authors.initials: P
authors.lastname: Woodhams
authors.forename: K
authors.initials: K
authors.lastname: Zilles
mesh_terms: D000818:Animals; D015415:Biomarkers; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000737:chemistry / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism; D008970:Molecular Weight; D016900:Neurofilament Proteins / Q000737:chemistry / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D003598:Cytoskeletal Proteins; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; D011509:Proteoglycans